# Transcription factors governing the development of GHRH-neurons

> **NIH NIH R01** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2021 · $547,873

## Abstract

The ultimate research goal of this lab is to decipher the gene regulatory network that directs the development of
various types of neurons in the mouse arcuate nucleus of the hypothalamus (ARC). Despite the physiological
significance of many ARC neurons, the developmental gene regulatory programs for ARC neurons remain poorly
understood. This lab has been pioneering this emerging area of studies by successfully combining mouse
genetics and genome-wide studies. Notably, a close developmental link has been discovered among different
types of ARC neurons. These intertwined developmental pathways are likely crucial to ensure the balanced
production of different ARC neurons during embryogenesis, enabling a highly coordinated regulation of various
homeostatic processes in later postnatal life, such as integration of feeding, reproduction, and growth.
 Key preliminary results in this grant include: i) Single cell RNA-seq (scRNA-seq) analyses reveal eight TFs
enriched in developing growth hormone-releasing hormone (GHRH)-neurons in the ARC, which control linear
growth; Prox1, Gsx1, Egr1, Foxp2, Pbx3, St18, Dlx1 and Dlx2. Notably, Dlx1/2, Foxp2 and Gsx1 have been
shown to be important for the development of GHRH-neurons, indicating that the scRNA-seq approach is highly
useful to identify TFs acting on neuronal lineage development. ii) GHRH-specific inactivation of Prox1 leads to
dwarfism and reduced Ghrh expression in mice. iii) Further, ChIP-seq data for Dlx1 provides various new insights
into the mechanism by which Dlx1 controls GHRH-neuronal development. Together, these results led to the
central hypothesis Dlx1/2 and Prox1 play vital roles in acquiring GHRH-neuronal fate over other related
ARC neuronal lineages in part by coordinating the expression of downstream TFs. This hypothesis will be
tested in the two specific aims using an ensemble of biochemical and cellular methods, mouse genetics and
genome-wide approaches. Completion of this innovative study will radically improve the understanding of how
common progenitors are guided to gain a specific ARC lineage identity over other related cell fates, providing a
critical mechanism contributing to the balanced production of diverse ARC neuronal types during development.

## Key facts

- **NIH application ID:** 10310822
- **Project number:** 1R01NS118748-01A1
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** JAE W LEE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $547,873
- **Award type:** 1
- **Project period:** 2021-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10310822

## Citation

> US National Institutes of Health, RePORTER application 10310822, Transcription factors governing the development of GHRH-neurons (1R01NS118748-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10310822. Licensed CC0.

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